The delivery of drugs through the skin provides many advantages; primarily, such a means of delivery is a comfortable, convenient and noninvasive way of administering drugs. The variable rates of absorption and metabolism encountered in oral treatment are avoided, and other inherent inconveniences -- e.g., gastrointestinal irritation and the like -- are eliminated as well. Transdermal drug delivery also makes possible a high degree of control over blood concentrations of any particular drug.
The vast majority of transdermal systems are designed so as to deliver a drug substantially continuously throughout the wearing period. For many drugs, however, continuous delivery poses the potential problem of drug tolerance. For such drugs, a continuous delivery patch must removed periodically during the wearing period so as to prevent development of tolerance. The inconvenience of periodic patch removal can in turn create problems with patient compliance and thus with drug efficacy as well.
One drug which is currently administered transdermally is nitroglycerin, a vasodilator useful in the treatment of angina pectoris and congestive heart failure. Several transdermal systems currently on the market provide continuous plasma levels of nitroglycerin over a 24-hour period (e.g., the "Transderm Nitro".RTM. system of ALZA Corporation, Palo Alto, California). However, there is increasing evidence that continuous delivery of nitroglycerin causes development of tolerance in the patient, with resulting loss of efficacy. Recently, this factor has caused certain regulatory authorities to advise against the use of delivery systems that will administer nitroglycerin continuously without a washout period at some time during the day
An additional problem which is common to most transdermal drug delivery systems is residual drug, i.e., drug which remains in the device after use. Highly expensive drugs are costly to discard, and dangerous or controlled narcotic drugs can be diverted for abuse or present other uncontrollable hazards
The present invention is addressed to these deficiencies in the art, and provides a system wherein (1) drug delivery is not continuous but biphasic, and (2) substantially no drug remains in the device after use.